A resource of 621 breast cancer families has been developed. This proposal will utilize the resource to generate information on the breast cancer risks for sistes and daughters of unselected patients as well as for sisters and daughters of patients selected for having a family history of the neoplasm. The resource will aso provide families with previously defined clinico-genetic entities, i.e., SBLA syndrome, breast-ovarian cancer, Cowden's disease, and site-specific breast cancer, all characterized by early-occurring and bilateral breast cancer, and Muir's syndrome, characterized by late onset of a variety of neoplasms including the breast. In addition to their association with breast cancer, these particular entities were chosen because they are examples of single locus conditions, they may involve associated identifying lesions, and as such they have relatively early ages at onset. Each entity will be evaluated for linkage between the disease allele and an array of polymorphic marker loci composed of cell surface antigens, plasma proteins, erythrocyte enzymes, and immunoglobulin types. A total of 70 families with these entities have been selected for the proposed linkage detection and estimation studies because of their multi-generational structure and size and segregation patterns of breast cancer. This proposal should thus help clarify the genetics of breast cancer, provide information on the organization of the human genome, and importantly, provide information of practical utility to the identification and detection of high risk individuals through linked markers prior to the onset of tumors.